Neurodegenerative Dementias and the Multidisciplinary ... · Clinical Presentation: Atypical. Age-related cognitive change DECLINE WITH AGE FREE RECALL (NO-CUE) Remembering items

Neurodegenerative Dementias

and the Multidisciplinary Approach

to Patient Care

Roberto Fernandez MD, MPH, PhD

Medical Director

The Pat Summitt Clinic

Brain and Spine Institute

University of Tennessee Medical Center

• Overview of Alzheimer’s disease and other age-related

dementias

• Diagnostic approach to dementia

• Multidisciplinary approach to dementia care

• The benefits of multidisciplinary care

Overview

• Alzheimer’s Disease

• Vascular Dementia

• Dementia with Lewy Bodies

• Frontotemporal Dementia

• Chronic Traumatic Encephalopathy

• Other (Metabolic, Autoimmune, Infectious)

Causes of Dementia

Dementia

Alzheimer’s in Numbers

The only top 10 cause of death that cannot

be prevented, effectively treated or cured

• Twice as likely to report financial, emotional and physical

difficulties compared to non-AD caregivers

• 30-40% suffer from clinical depression

• Risk of depression is 2x higher

Caregiver Burden

6

• Impairment of recent episodic memory is most common

early symptom.

• Working memory and semantic memory initially

preserved

• Non-amnestic symptoms are frequent and may precede

memory deficits (visuospatial, language, apraxia,

dysexecutive, behavioral)

• Neuropsychiatric symptoms include apathy, anxiety,

irritability and depression

• Hallucinations, delusions and disinhibition occur later, but

can also happen sooner in behavioral variant

Clinical Presentation: Typical

7

• Frontal variant:

– Early personality change out of proportion to cognitive impairment

– Irritability, impulsivity and disinhibiton

• Posterior cortical atrophy:

– Visuospatial and visuo-perceptual impairments

– Bálint’s syndrome (simultagnosia, oculomotor apraxia, optic ataxia)

– Gerstmann’s Syndrome (agraphia, acalculia, finger agnosia, left-right disorientation)

– Deficits in working memory

• Logopenic variant of primary progressive aphasia:

– Confrontation anomia and impaired repetition with preserved grammar and no speech apraxia

• Corticobasal syndrome:

– Apraxia, parkinsonism, visuospatial deficits

Clinical Presentation: Atypical

Age-related cognitive change

DECLINE WITH AGE

FREE RECALL (NO-CUE) Remembering items on a shopping list

SOURCE OF MEMORYRecalling where or in what circumstances a fact was

learned

PROSPECTIVE MEMORYRemembering to take a medication before going to

bed

PROCESSING SPEED Time to complete tasks, reaction times

ATTENTION Divided selective, and sustained attention

EXECUTIVE FUNCTIONAbstraction, mental flexibility, concept formation

decline after age 70. Response inhibition.

CONSTRUCTIONALConstructional abilities and learning new tasks can

decline

Age-related cognitive change

STABLE WITH AGE

RECOGNITION MEMORYRetrieving memory when given a cue (e.g. recalling

details of a story when asked yes/no questions)

TEMPORAL ORDER Recalling the sequence of events

PROCEDURAL MEMORY How to tie a shoe lace, ride a bike

LANGUAGE

Overall intact with aging. Vocabulary may improve.

Some decline in confrontational naming and word

search. Sporadic word finding difficulty.

VISUOSPATIALNavigation, orientation, depth perception tend to

remain Intact

10

Pathology: Amyloid Plaques

• Amyloid is a naturally occurring

protein

• In it’s abnormal form, it has tendency

to aggregate forming plaques

Image: wiki.brown.edu

Amyloid Plaques Tau Tangles

• Normal tau protein plays crucial role

in neuronal structure and function

• In AD and several other dementias,

Tau changes its configuration, forms

tangles, cause cell dysfunction and

eventually cell death

•

11

Pathology: Anatomical Distribution

• Not all brain regions are

affected equally or at the

same time

• Some areas are more

vulnerable

• Hallmark changes are

first seen in temporal

lobes

• Other brain regions may

be affected first

• Spreads in a predictable

pattern Images: www.alz.org

Pathology: Genetics

• APOE4 is a variant of a gene that has been established

as the most common genetic risk factor for sporadic

Alzheimer’s of late onset (usually after age 65)

• Presence of one or two copies of this gene increases the

risk of Alzheimer’s but it is also a poor predictor of who

will or will not get the disease

• Familial, autosomal dominant, early onset forms of the

disease (e.g. Presenilin 1 mutation) are very rare and

account for less than 2% of cases

• There are currently no approved medications that can cure, slow down or revert Alzheimer’s

• Approved medications are intended to treat symptoms and may provide temporary improvement– Donepezil (Aricept), rivastigmine (Exelon)– Memantine (Namenda)

• Non-pharmacological interventions can improve quality of life and may slow down progression (diet, exercise, social interaction, and caregiver support)

• Experimental drugs target know mechanism of disease through different approaches

Treatment Strategies

• Healthy lifestyle may slow cognitive decline and may

reduce risk of developing dementia

• Study from Lancet showed evidence that a number of

dementias (up to 1/3) may be preventable and that the

risk can be significantly reduced by risk factor

modification at different stages in life:

• Early life - Level of education

• Middle life - Hypertension, hearing loss and obesity

• Late life - smoking cessation, treating depression,

increased physical activity, social interaction,

diabetes

Preventive Measures

Some Recommendations

• Participate in intellectually engaging activities and maintain social interactions

• Routine physical activity, especially exercise that improves cardiovascular health

• Maintain a heart-healthy diet

• Maintain healthy sleep habits and treat sleep conditions such as sleep apnea

• Minimize alcohol use and do not smoke

• Diverse group of syndromes

• Characterized by focal degeneration in the frontal and anterior

temporal lobe

• Typically presents with behavioral symptoms, language impairments,

or both

• Patients may also have motor symptoms and may develop other

neurodegenerative diseases such as ALS

• In contrast with Alzheimer’s, there are multiple types of pathological

types, with different abnormal proteins

Frontotemporal Lobar Degeneration

Frontotemporal Lobar Degeneration

• Third most common cause of neurodegenerative dementia after AD

and DLB

• Prevalence close to AD 60-70

• Age of onset 45-65

• Median survival ranges from 2-8

Behavioral Variant

Primary

Progressive

Aphasia

Progressive non-

fluent aphasia

Semantic

Dementia

Logopenic

Variant

Behavioral Variant

• Insidious onset of changes in social decorum and personal regulation

including:✓ Apathy

✓ Overeating

✓ Emotional blunting

✓ Loss of empathy

✓ Personality changes: Coldness and Submissiveness

✓ Repetitive motor behaviors, ritualistic behaviors

✓ Impairment of judgment and insight

✓ Inappropriate behaviors and disinhibition

• Deficits in executive control as reflected by difficulties performing

tasks such as:

✓ Organization

✓ Planning

✓ Multitasking

✓ Disengaging from specific activities

✓ Generating ideas

• Behavioral symptoms are very common in other dementias.

Behavioral and personality changes do-not equal FTD

Primary Progressive Aphasia

Group of clinical syndromes with

diverse pathology

Most prominent clinical feature

is difficulty with language

These deficits are the principal

cause of impaired function

Distinct brain regions affected in

each variant

Logopenic variant tends to be a

language variant of Alzheimer’s

Non-fluent

Semantic

Logopenic

Non-Fluent Aphasia

• Patients speak in simple phrases, with

grammatical errors (e. g. errors in tense, use

of prepositions)

• Effortful speech: Slow, labored speech

production

• Mispronunciation of words and errors in

sequencing of syllables

“aminal” for “animal”

“Sable” for “Table”

• Phrases are short, generally less than 4

words

• Inferior frontal and left antero-superior

temporal atrophy

Semantic Dementia

• Difficulty naming objects and comprehension

of single words with fluent speech and

preserved grammar

• Patients often repeat the word and ask what

it means

• May have difficulty interpreting facial

expressions of emotion and recognizing

familiar faces

OTHER M ETHODS OF DIAGNOSIS

Elect rophysio log ic M et hods

Electrophysiologic methods have not

been extensivelystudied in FTD, but EEG

patterns can differentiate FTD from AD

with an accuracy ranging between 85%

and 93% (Table 10-7).53 In one study,

a group of subjects with pathologically

proven late-onset FTD had normal EEGs,

while in those with early-onset FTD the

EEGsweremildlyand variablyabnormal.54

CSF M arkers

CSFmeasurementsof tau and A -amyloid

appear promising for differentiating FTD

from AD. CSF tau and the ratio of tau/

A 42are significantly lower in FTD than

in AD. The tau/A 42 ratio discriminated

between FTD and AD with a sensitivity

of 79% to 90% and a specificity of 65%

to 97%.55

TREATM ENT

Management of FTD is currently symp-

tomatic. No treatments have been ap-

proved, but selective serotonin reuptake

inhibitors can decrease disinhibition,

overeating, and repetitive behaviors.

Low dosesof trazodone or atypical anti-

psychoticscan help with agitation. Cho-

linesterase inhibitors are not recom-

mended for FTD becausetheymaycause

agitation. Memantine is under investiga-

tion for use in FTD. Nonpharmacologic

approaches such as support groups for

caregivers and behavioral interventions

are recommended.

Increased knowledge about the mo-

lecular mechanisms in FTD has identi-

fied targets for new treatments, such as

the tau or TDP43 proteins. Among the

Continuum Lifelong Learning Neurol 2010;16(2)

207

FIGURE 10-5 Atrophy distribution involves differentregions in semantic variant andprogressive nonfluent aphasia. The left

image shows left perisylvian atrophy and relatively preservedtemporal lobe in a patient with progressive nonfluentaphasia. Right, A coronal MRI image from a patient withsemantic variant displays severe atrophy of temporal regionsalong with relatively preserved frontal lobes.

FIGURE 10-6 T1-weighted MRI images (coronal slices)and axial single-photon emissioncomputed tomography (SPECT) images in a

patient with corticobasal degeneration. Top, MRI indicatesbilateral frontal and parietal atrophy, and (bottom) SPECTshows asymmetric left-sided frontoparietal and basalganglia hypoperfusion.

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

• Right side: Prosopagnosia, some degree of anomia, mild loss of object

knowledge. Often present behavioral symptoms similar to bvFTD

• Left side: Fluent aphasia beginning with profound anomia, later

progressing to globally impaired knowledge of objects (what they do,

where they are found, etc)

Treatment of FTD Syndromes

• Management of inappropriate or aggressive behavior with non-

pharmacological measures when possible

• Discussion of tolerance for disruptive but non-dangerous behavior

• Speech therapy for language variants

• Some types of antidepressants may help with some behaviors

• Atypical antipsychotics have risks but may be necessary

• No evidence to support use of Alzheimer’s medications and in fact

they may worsen symptoms and cognitive function

Dementia With Lewy Bodies (DLB)

• Third most common type of adult onset dementia after AD and

vascular

• Difficulties with attention, executive function and visual-spatial function

• Difficulties with memory that tend to improve with cuing

• Frequent hallucinations

• Rapid fluctuations in cognitive function (minutes or hours)

• REM behavior disorder

• Parkinsonism

• Can respond favorably to cholinesterase inhibitors (e.g. donepezil)

Diagnostic Approach to Dementia

History Physical

Exam

Diagnostic

Studies Pathology

• Clinical history is most important

• Neurologic Exam

• Cognitive testing

– Screening tests

– Comprehensive neuropsychological testing

• Brain Imaging (MRI or CT scan)

• Spinal fluid markers or PET scans in complex cases (not routinely done)

Diagnostic Approach to Dementia

26

Structural: CT and MRI

Functional: FDG-PET

Amyloid PET

CSF Aß and Tau

Biomarkers

Multidisciplinary Care Model

Multidisciplinary Team

Behavioral Neurologists

Roberto Fernandez, MD, MPH, PhD

Bruce R. LeForce, MD

Mary Widmeyer, MD

Lauren McCollum, MD

Clinical Neuropsychologists

Malcolm D. Spica, PhD

Nichole K. Miller, Psy. D

Nurse Practitioner

Heather Massengill, NP

Nurse Coordinator

Jan Alexander, RN

Social Worker

Sallie W. Gentry, LCSW, CCM

Charlotte Sorensen, MSW

Speech-Language Pathologist

Mandie Oslund, MS, CF-CSP

Social Work

CareCoordination

Clinical ResearchPT/OT/SLNeuro-

Psychology

Nurse Practitioner

Nurse

Coordinator

Neurology

Patient&

Family

Cognitive Testers

Sydney Michelson

Taylor Leonard

Medical Assistants

Elaine Leonard

Megan Pierce

Clinical Care

• Comprehensive extended visits

• Individualized care focused on patient and

caregivers

• Standardized cognitive testing performed

at each visit

• Multidisciplinary team involvement

• Comprehensive neuropsychological testing

• Specialized cutting edge diagnostic

techniques

• Care coordination and caregiver support

• Clinical and basic science research

• Durable medical

equipment

• Therapy, PT, OT, Speech

• Patient letters

• In-home care

• Hospice/Palliative care

• Capacity questions

• Elder abuse

• Patient assistance

programs

• Caregiver support

• Educational programs

• Support Groups

• Transportation

• Housing

• Power of Attorney/Living

wills

• Driving Concerns

• Community resources

• Placement

Social Work

Nurse Coordinator

• Visit with all new patients to review plan, offer visit summary and any

additional individualized teaching and educational materials as indicated

by provider

• Meets with follow-up patients as needed when new interventions or

changes in management are implemented

• Maintain information of ongoing clinical trials and other research studies

and discuss with patients and families who are interested in possible

participation

• Follow up telephone calls to families and patients with information and

support as needed regarding test results, caregiver support and

questions, and medications

• Coordination of communication between physician and patient, families,

health care team

Neuropsychological evaluations:

– Designed to identify the extent & severity of a person’s cognitive and

behavioral impairments

– Help determine a person’s areas of cognitive strength/weakness

– Help assess patients capacity for decision making

– Use standardized tests to evaluate cognitive abilities such as:

• Attention

• Memory

• Language

• Processing speed

• Visuospatial function

• Planning and Organization

- Not all patients are candidates for full testing. Indication and extent of

testing is determined by behavioral neurologist at time of referral

Neuropsychology

• Time for provider to meet separately with

caregivers and with patient

• Brief standardized cognitive screeners (MoCA and

Cognivue)

• Administration of multiple diagnostic instruments

for assessment of depression, anxiety, caregiver

strain and ADLs

• Caregiver meeting with Social Work

• Visit with Nurse Coordinator to review plan and

education

• Patient and family should plan for a 3 hour visit

• Diagnostic work-up: May include brain imaging,

full neuropsychological testing, blood work and

advanced diagnostics in very specific cases (e.g.

CSF biomarkers, PET imaging)

Initial Visit

• Review of work-up

results

• Discussion of diagnosis

• Addressing treatment

and plan of care with

provider and Social

Work

• Meeting with nurse

coordinator as needed

Follow-up Visits

• Usually every 6 months

• May alternate with MLP (patients will see neurologist at least once a year)

• Repeat brief neuropsychological testing at 6 month intervals

• Meeting with nurse coordinator and/or Social Worker as needed

Diagnostic Follow-up Routine Follow-up

Savvy Caregiver Program

• Program intended to train caregivers in the

basic knowledge, skills and attitudes needed

to handle the challenges of caring for family

members with dementia

• 12 hours of training, divided in 2 hour

sessions over 6 weeks

• A total of 20 caregivers have been trained

• Respite care provided for patients

• High satisfaction and impact according to

surveys

• We will continue to offer this program several

times a year

Benefits of Multidisciplinary Care

• Timely and accurate diagnosis

• Personalized treatment and plan of care

• Optimized treatment tailored to condition and stage of disease

• Access to educational resources

• Access to support resources

• Opportunities for participation in clinical trials and research studies

• Helps facilitate transitions through the course of disease and end of life

• Improve patient outcomes

• Decrease hospitalizations and delays in institutionalization

• Increase patient satisfaction

• Decreases unnecessary health care

• Improves patient and caregiver quality of life.

• Reduces caregiver burden

• Increases independence

2nd Annual Symposium

Nicole Dawson

PT, PhD

Save the Date!May 7-8, 2020

Ronald Petersen

MD, PhDTyler Summitt

Downtown Knoxville

“Put the team before yourself”From Pat Summitt’s Definite Dozen

Thank You